Affinage

Showing TYROBP — DAP12 is a alias.

TYROBP

TYRO protein tyrosine kinase-binding protein · UniProt O43914

Length
113 aa
Mass
12.2 kDa
Annotated
2026-06-10
100 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TYROBP (DAP12) is a disulfide-bonded homodimeric transmembrane adaptor protein that couples a broad repertoire of non-covalently associated cell-surface receptors to activating tyrosine-kinase signaling in NK cells, myeloid cells, and microglia (PMID:9490415, PMID:9852069). Receptor partners associate through reciprocal charged transmembrane residues, and this pairing both stabilizes receptor surface expression and licenses signaling; documented partners include activating KIRs, CD94/NKG2C, mouse Ly-49D/H, the myeloid receptors TREM2, TREM1, SIRPβ1, MDL-1, Siglec-15, and plexin-A1, as well as integrin αvβ3 and the M-CSF receptor c-Fms (PMID:9490415, PMID:9655483, PMID:9647200, PMID:11602640, PMID:10449773, PMID:10940905, PMID:18691974, PMID:22451653, PMID:25547154). Upon receptor engagement, Src-family kinases (Fyn, Lck, Fgr) phosphorylate the DAP12 cytoplasmic ITAM, whose intact tyrosines are essential for function; phospho-ITAM then recruits Syk (dominantly over ZAP-70) to drive PLCγ, ERK/MAPK, calcium mobilization, PI3K, and β-catenin signaling, while CD45 dephosphorylates DAP12 and SHIP1 binds phospho-DAP12 to restrain PI3K recruitment (PMID:9852069, PMID:9830044, PMID:16709819, PMID:19503107, PMID:20484116). Through these pathways DAP12 controls NK cytotoxicity, osteoclast multinucleation and cytoskeletal organization, macrophage fusion and proliferation, and microglial regulation of synaptic function (PMID:11021533, PMID:14969392, PMID:15073337, PMID:18957693, PMID:19503107, PMID:15601948). Its expression is directly driven by the myeloid transcription factor PU.1 (PMID:17827340). Loss-of-function mutations in TYROBP cause Nasu-Hakola disease (PLOSL) through failure of osteoclast and microglial/oligodendrocyte function (PMID:10888890, PMID:12569157, PMID:12925681), and in mouse Alzheimer's and tauopathy models TYROBP deficiency reduces complement C1q and preserves synaptic and cognitive function (PMID:28612290, PMID:30283031).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1998 High

    Established DAP12 as an ITAM-bearing homodimeric adaptor that physically couples ITIM-less activating receptors to the Syk/ZAP-70 kinases, defining the core activation logic of the protein.

    Evidence Co-IP, crosslinking activation, and phosphopeptide binding to ZAP-70/Syk; plus mutagenesis showing TM charged residues mediate NKG2C and Ly-49 association and surface expression

    PMID:9490415 PMID:9647200 PMID:9655483

    Open questions at the time
    • Did not resolve which Syk-family kinase dominates in vivo
    • Did not define downstream effectors beyond kinase recruitment
  2. 1998 High

    Pinpointed the ITAM tyrosines as the functionally essential signaling motif and identified Syk, not ZAP-70, as the dominant downstream kinase driving PLCγ, MAPK, and calcium flux.

    Evidence ITAM point mutagenesis in transfection assays and dominant-negative Syk vs. ZAP-70 in NK-cell calcium mobilization

    PMID:9830044 PMID:9852069

    Open questions at the time
    • Did not identify the kinase phosphorylating the ITAM
    • Did not address cell-type-specific use of ZAP-70
  3. 2000 High

    Linked TYROBP loss-of-function to a human Mendelian disease, demonstrating the physiological consequence of abolishing DAP12 signaling.

    Evidence Positional cloning and mutation characterization of null alleles in Nasu-Hakola/PLOSL patients

    PMID:10888890

    Open questions at the time
    • Did not identify the cell types whose dysfunction produces bone and brain pathology
    • Did not define the relevant receptor partner in disease
  4. 2000 High

    Expanded the receptor repertoire to myeloid lineages (MDL-1, SIRPβ1) and distinguished DAP12 from DAP10, showing ITAM/Syk versus YxNM/PI3K specialization that synergize.

    Evidence DAP12-association cDNA screens, Co-IP in transfectants and primary monocytes, TM-domain specificity and synergy assays

    PMID:10449773 PMID:10604985 PMID:10940905 PMID:11015446

    Open questions at the time
    • Did not establish in vivo relevance of each myeloid partner
    • DAP10/DAP12 crosstalk mechanism not fully resolved
  5. 2000 High

    In vivo ITAM-specific knock-in and knockout mice revealed dedicated roles in NK cytotoxicity, dendritic-cell homeostasis, and antigen-presenting-cell function distinct from other ITAM adaptors.

    Evidence DAP12-/- and ITAM-mutant knock-in mice with NK cytotoxicity, DC quantification, EAE, and contact-sensitivity assays

    PMID:11021532 PMID:11021533 PMID:11602640

    Open questions at the time
    • Did not connect immune phenotypes to the disease-relevant bone/brain functions
    • Receptor responsible for each phenotype not always defined
  6. 2003 High

    Identified the osteoclast and CNS cell-type basis of Nasu-Hakola disease, establishing DAP12 (with TREM2) as essential for osteoclast differentiation, multinucleation, and bone resorption.

    Evidence DAP12-/- mouse phenotyping, patient-derived PBMC osteoclast differentiation, and retroviral DAP12 rescue of multinucleation

    PMID:12569157 PMID:12925681 PMID:14969392

    Open questions at the time
    • Did not resolve whether the defect is in differentiation versus cytoskeletal function
    • Downstream effectors of multinucleation incompletely mapped
  7. 2004 High

    Defined DAP12 as a microglia-restricted CNS adaptor that regulates synaptic function and showed ITAM/Syk redundancy with FcRγ in osteoclast development.

    Evidence Cell-type immunolabeling and synaptic electrophysiology/fractionation in DAP12-/- brain; DAP12/FcRγ double-KO osteoclast reconstitution with mutant constructs; plexin-A1–TREM2 Co-IP

    PMID:15073337 PMID:15601948 PMID:16715077

    Open questions at the time
    • Mechanism by which microglial DAP12 alters neuronal synapses not defined
    • Functional partition between DAP12 and FcRγ unresolved
  8. 2006 High

    Completed the kinase circuit by identifying Src-family kinases (Fyn, Lck) as the DAP12 ITAM kinases and CD45 as the phosphatase that tunes signaling magnitude.

    Evidence Co-IP of Fyn/Lck with the Ly-49D/DAP12 complex, Src inhibitor and Fyn/Lck KO NK cells, and CD45-null NK-cell hyperphosphorylation analysis

    PMID:16709819

    Open questions at the time
    • Did not determine receptor-specific kinase preferences
    • Spatiotemporal coordination of kinase/phosphatase not resolved
  9. 2008 High

    Embedded DAP12 within growth-factor and integrin signaling, establishing the c-Fms→c-Src(Y559)→DAP12→Syk→cytoskeleton axis and roles in macrophage fusion and slow leukocyte rolling.

    Evidence Co-IP and site-directed mutagenesis of c-Fms Y559 and DAP12 ITAM/TM with reconstitution; TREM2/Syk-dependent macrophage fusion assays; Tyrobp-/-Fcrg-/- neutrophil rolling and intravital studies

    PMID:18691974 PMID:18794338 PMID:18957693

    Open questions at the time
    • How phospho-DAP12 reorganizes the cytoskeleton mechanistically not detailed
    • Relative contribution of DAP12 vs FcRγ in rolling not fully partitioned
  10. 2009 High

    Demonstrated DAP12 controls myeloid/microglial proliferation and survival via M-CSF→CSF-1R→β-catenin signaling, extending its role beyond receptor-triggered activation.

    Evidence DAP12-/- macrophage proliferation/survival assays, β-catenin phosphorylation and nuclear translocation, bone marrow transplantation, microglial quantification

    PMID:19503107

    Open questions at the time
    • Direct biochemical link between DAP12 and β-catenin not fully resolved
    • Receptor partner for proliferative signaling not defined
  11. 2010 High

    Resolved the differentiation-versus-function debate in osteoclasts and mapped positive (PI3K via DAP10) and negative (SHIP1) regulators of the TREM2-DAP12 module.

    Evidence DAP12-/- osteoclast/osteoblast co-culture with OSCAR rescue; TREM2 ligation assays with DAP10-PI3K recruitment and SHIP1 SH2-mutant Co-IP

    PMID:20484116 PMID:20720152

    Open questions at the time
    • Precise step in transmigration blocked by cytoskeletal defect not defined
    • Stoichiometry of TREM2/DAP12/DAP10/SHIP1 complex unknown
  12. 2011 High

    Revealed context-dependent inhibitory signaling, with DAP12 recruiting SHP-1 (via MAIR-II) to dampen B-cell activation and maintaining dendritic-cell immaturity, alongside Btk as a positive amplifier of TREM-1/DAP12.

    Evidence DAP12-/- and MAIR-II chimeric receptor B-cell assays with SHP-1 Co-IP; DAP12 siRNA in liver DCs with STAT3/IRAK-M readouts; Btk knockdown/mutant analysis in TREM-1/DAP12 signaling

    PMID:21257958 PMID:21659545 PMID:21727189

    Open questions at the time
    • Molecular switch between activating and inhibitory DAP12 outputs not defined
    • Liver DC finding rests on siRNA in a single system
  13. 2012 High

    Identified Siglec-15 as a DAP12 partner that couples sialoglycan recognition to Syk-driven osteoclastogenesis and to immunosuppressive TGF-β production in macrophages.

    Evidence TM lysine mutagenesis (K272/K274) abolishing DAP12 association, Syk Co-IP, knockdown, and chimeric rescue with multinucleation, bone-resorption, and TGF-β readouts

    PMID:22451653 PMID:23035012

    Open questions at the time
    • In vivo contribution of Siglec-15/DAP12 to tumor immunity not established here
    • Integration with RANK-NFAT2 pathway only partially mapped
  14. 2014 High

    Established integrin αvβ3 as a DAP12 activator in osteoclasts through genetic epistasis, refining the receptor inputs that drive osteoclast cytoskeletal function.

    Evidence αvβ3/DAP12 double-KO mice with Syk phosphorylation assays and OSCAR rescue experiments

    PMID:25547154

    Open questions at the time
    • Direct physical coupling of integrin to DAP12 not biochemically detailed
    • Generalizability beyond osteoclasts unknown
  15. 2015 High

    Defined DAP12 as a downstream effector in microglial neuropathic-pain signaling, dissociating pain-gene induction from CSF1R-driven proliferation, and stabilizer of the TREM2 C-terminal fragment.

    Evidence DAP12-/- mice in nerve injury and intrathecal CSF1 pain models; co-expression and interaction-mutant analysis of TREM2-CTF stabilization with LPS inflammatory readouts; alveolar macrophage IRI/CXCL2 studies

    PMID:25762783 PMID:25957402 PMID:26642091

    Open questions at the time
    • Receptor driving pain-gene induction not fully defined
    • Functional consequence of TREM2-CTF stabilization in vivo unclear
  16. 2017 High

    Demonstrated that TYROBP deficiency is neuroprotective in Alzheimer's and tauopathy models, implicating microglial DAP12 in disease-promoting complement and inflammatory responses.

    Evidence APP/PSEN1;Tyrobp-/- and MAPTP301S;Tyrobp-/- mice with electrophysiology, behavior, C1q immunohistochemistry, and transcriptomics; TREM2/DAP12 anti-inflammatory JNK-pathway and pain studies

    PMID:27798193 PMID:28612290 PMID:28680398 PMID:30283031

    Open questions at the time
    • Dissociation of C1q reduction from tau pathology mechanistically unresolved
    • Whether protection is microglia-intrinsic not fully established
  17. 2023 Medium

    Human single-nucleus transcriptomics revealed a distinct DAP12-deficient microglial wound-healing signature in Nasu-Hakola brains not recapitulated in mice, indicating human-specific pathology.

    Evidence snRNA-seq of human NHD brain specimens with RUNX1/STAT3/TGF-β pathway signatures, compared to DAP12-deficient mouse brain

    PMID:36658241

    Open questions at the time
    • Transcriptomic correlation without mechanistic reconstitution
    • Cause of human-mouse divergence not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single ITAM adaptor switches between activating (Syk-driven) and inhibitory (SHP-1/SHIP1-driven) outputs across cell types and receptor pairings, and how this is exploited therapeutically, remains unresolved.
  • No unified model of context-dependent DAP12 output
  • No structural model of receptor/DAP12/kinase assembly
  • Human-specific NHD pathology mechanism undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4
Partners
FYNINPP5DNKG2CSIGLEC15SIRPB1SYKTREM1TREM2
Complex memberships
CD94/NKG2C-DAP12 complexSiglec-15-DAP12 complexTREM2-DAP12 receptor complex

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 DAP12 (TYROBP) is a disulfide-bonded homodimer containing an ITAM in its cytoplasmic domain that non-covalently associates with KIR family members lacking ITIM sequences. Crosslinking of KIR-DAP12 complexes induces tyrosine phosphorylation of cellular proteins and upregulation of early-activation antigens. Phosphorylated DAP12 peptides bind ZAP-70 and Syk protein tyrosine kinases. Co-immunoprecipitation, crosslinking activation assay, phosphopeptide binding assay with ZAP-70 and Syk Nature High 9490415
1998 CD94/NKG2C, an activating NK cell receptor, non-covalently associates with DAP12. Charged residues in the transmembrane domains of DAP12 and NKG2C are necessary for their interaction, and efficient cell-surface expression of CD94/NKG2C requires the presence of DAP12. Co-transfection, surface expression assay, co-immunoprecipitation, transmembrane domain mutagenesis Immunity High 9655483
1998 Ly-49D and Ly-49H (mouse NK receptors lacking ITIM) associate with mouse DAP12. Co-transfection of either receptor with DAP12 induces surface expression of both proteins; their complex was co-immunoprecipitated. Stimulation of the Ly-49/DAP12 complex results in tyrosine phosphorylation of multiple cellular substrates. Co-transfection, co-immunoprecipitation, anti-receptor crosslinking with tyrosine phosphorylation readout Journal of Immunology High 9647200
1998 DAP12's signal transduction function depends on the integrity of its intracytoplasmic ITAM, as shown by point mutation studies. DAP12 is expressed ubiquitously on hematopoietic and non-hematopoietic cells. Point mutation of ITAM tyrosines, transfection assay, Northern blot/expression analysis The Journal of Biological Chemistry High 9852069
1998 DAP12-mediated signaling in NK cells proceeds dominantly through Syk, not ZAP-70. Ligation of Ly-49D/DAP12 results in phosphorylation of PLCγ1, Cbl, and p44/p42 MAPK, and calcium mobilization; dominant negative Syk but not catalytically inactive ZAP-70 blocks calcium mobilization. In vitro kinase assay, dominant-negative overexpression, calcium mobilization assay, immunoprecipitation/Western blot The Journal of Biological Chemistry High 9830044
2000 Loss-of-function mutations in TYROBP (DAP12) in humans cause polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL/Nasu-Hakola disease). One large deletion (Finnish alleles) and one point mutation (Japanese patient) were identified, both representing null alleles. Positional cloning, deletion/mutation characterization, patient genotyping Nature Genetics High 10888890
2000 DAP10 and DAP12 form distinct receptor complexes in NK cells despite their similarities. The transmembrane regions of DAP10 and DAP12 are sufficient to confer specific association with their respective ligand-binding partners. DAP12 activates Syk/ZAP70 tyrosine kinases via its ITAM, while DAP10 activates PI3K via its YxNM motif; synergy between the two pathways enhances cytokine production. Co-transfection specificity assays, retroviral reconstitution, functional crosslinking, kinase activation assays The Journal of Experimental Medicine High 11015446
2001 TREM-2 is a DAP12-associated cell surface receptor on human monocyte-derived dendritic cells. TREM-2/DAP12 signaling promotes upregulation of CCR7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and ERK, independently of NF-κB and p38 MAPK. Co-immunoprecipitation, receptor crosslinking, kinase activation assays (ERK, PTK), survival assays, signaling pathway inhibitor studies The Journal of Experimental Medicine High 11602640
2000 In DAP12-deficient mice, activating Ly49 receptors on NK cells are downregulated and non-functional; the mice are resistant to experimental autoimmune encephalomyelitis (EAE) due to strongly diminished IFN-γ production by myelin-reactive CD4+ T cells caused by inadequate T cell priming in vivo. Targeted gene disruption (DAP12-/- mice), EAE induction, flow cytometry, cytokine assays Immunity High 11021532
2000 KARAP/DAP12 knock-in mice bearing a non-functional ITAM show restricted NK cell natural cytotoxicity and dramatic accumulation of dendritic cells in mucocutaneous epithelia with impaired hapten-specific contact sensitivity, demonstrating specific roles in innate immunity distinct from CD3ζ and FcRγ. Knock-in mice with ITAM mutation, NK cytotoxicity assays, DC quantification, contact hypersensitivity model Immunity High 11021533
2000 MDL-1 (myeloid DAP12-associating lectin-1), a type II transmembrane C-type lectin exclusively expressed on monocytes/macrophages, associates with DAP12 via a charged residue in its transmembrane domain. Crosslinking of MDL-1/DAP12 complexes results in calcium mobilization. cDNA library screen exploiting DAP12 transmembrane property, co-expression/surface assay, calcium flux assay Proceedings of the National Academy of Sciences of the United States of America Medium 10449773
2000 SIRPβ1 associates with KARAP/DAP12 in an oligomeric complex in hematopoietic and non-hematopoietic transfectant cells and in human monocytes. This physical association couples SIRPβ1 engagement to recruitment of Syk and serotonin release. Co-immunoprecipitation in transfectants and primary monocytes, Syk recruitment assay, RBL cell serotonin release assay European Journal of Immunology High 10940905
2000 SIRPβ1 is expressed in monocytes and dendritic cells and associates with DAP12. SIRPβ1/DAP12 complex formation is required for efficient cell-surface expression of SIRPβ1. Stimulation of this complex induces tyrosine phosphorylation, MAPK activation, and cellular activation. mAb-based expression analysis, co-immunoprecipitation, activation assays (tyrosine phosphorylation, MAPK) Journal of Immunology High 10604985
2003 DAP12-deficient mice develop osteopetrosis and thalamic hypomyelinosis with synaptic degeneration. In vitro osteoclast induction from DAP12-/- bone marrow yielded immature cells with attenuated bone resorption; immature oligodendrocytes were arrested near the thalamus, indicating primary developmental arrest of both osteoclasts and oligodendrocytes. DAP12-/- mouse phenotyping, in vitro osteoclast differentiation, histology, electrophysiology (prepulse inhibition), immunohistochemistry The Journal of Clinical Investigation High 12569157
2003 Loss-of-function mutations in both DAP12 and TREM2 in PLOSL patients result in inefficient and delayed differentiation of peripheral blood mononuclear cells into osteoclasts with markedly reduced bone resorption capability in vitro, placing the DAP12-TREM2 complex as essential for osteoclast differentiation and function. In vitro osteoclast differentiation from patient-derived PBMCs, bone resorption assay The Journal of Experimental Medicine High 12925681
2003 DAP12 signaling is required for multinucleation during osteoclast development. DAP12-/- osteoclasts develop in vitro as intensely TRACP+ mononuclear cells and fail to generate multinuclear osteoclasts. Retroviral transduction of wild-type DAP12 into DAP12-/- precursors rescues in vitro osteoclast multinucleation. TREM2 was identified as the major DAP12-associated receptor in osteoclasts. DAP12-/- mouse osteoclast culture, retroviral rescue with wild-type DAP12, RT-PCR for DAP12-associated receptors, microCT bone density Journal of Bone and Mineral Research High 14969392
2004 DAP12 and FcRγ are ITAM-bearing adaptors required for functional osteoclast development. Mice lacking both adaptors are severely osteopetrotic; DAP12-/-FcRγ-/- bone marrow cells fail to differentiate into multinucleated osteoclasts or resorb bone, with impaired Syk phosphorylation. The SH2 domains of Syk and the ITAM tyrosines of DAP12 are required for reconstitution of function. Double-KO mouse model, in vitro osteoclastogenesis, bone resorption assay, Syk phosphorylation assay, retroviral transduction with wild-type/mutant constructs, epistasis Proceedings of the National Academy of Sciences of the United States of America High 15073337
2004 KARAP/DAP12 is expressed exclusively in microglia (not neurons, astrocytes, or oligodendrocytes) in the CNS. DAP12-deficient mice show enhanced LTP that is partly NMDA receptor-independent, decreased GluR2 subunit expression in postsynaptic densities, increased rectification of AMPA receptor EPSCs, and dramatically decreased synaptic TrkB without changes in whole-membrane fraction, indicating DAP12-dependent microglial regulation of synaptic function. Cell-type-specific immunolabeling, LTP electrophysiology, AMPA/NMDA receptor functional assays, biochemical fractionation of synaptic proteins, Western blot The Journal of Neuroscience High 15601948
2004 Plexin-A1 associates with TREM-2, linking semaphorin signaling to the ITAM-bearing adaptor protein DAP12. Plexin-A1-deficient mice show defects in immune responses and bone homeostasis. Plexin-A1-/- mouse generation, co-immunoprecipitation of plexin-A1 with TREM-2/DAP12, phenotypic analysis Nature Cell Biology Medium 16715077
2006 Src-family kinases Fyn and Lck are physically associated with the Ly-49D/DAP12 complex and are capable of phosphorylating DAP12. Inhibition of Src family kinases suppresses DAP12 phosphorylation and downstream signals. CD45 null NK cells show hyperphosphorylation of DAP12 and defective calcium mobilization and cytokine production upon Ly-49D ligation, indicating CD45 dephosphorylates DAP12 to coordinate signaling. Src kinase inhibitor studies, co-immunoprecipitation of Fyn/Lck with DAP12, Fyn-/- and Fyn/Lck double-KO NK cell assays, CD45-null NK cell analysis, calcium mobilization and cytokine assays Journal of Immunology High 16709819
2008 M-CSF binding to c-Fms generates a signaling complex comprising phosphorylated DAP12 and Syk. c-Fms tyrosine 559 (the exclusive binding site for c-Src) is necessary for DAP12/Syk signaling and osteoclast cytoskeletal reorganization. The SH2 domain of Syk and the ITAM tyrosines and transmembrane domain of DAP12 mediate this M-CSF signaling, establishing an epistatic pathway: c-Fms → c-Src (Y559) → DAP12 → Syk → cytoskeleton. Co-immunoprecipitation, site-directed mutagenesis of c-Fms Y559 and DAP12 ITAM/TM domain, retroviral transduction of null precursors with wild-type/mutant constructs, cytoskeletal assays Molecular Cell High 18691974
2008 DAP12 signaling through TREM-2 and downstream Syk is required for cytokine-induced macrophage fusion into multinucleated giant cells. Overexpression of DAP12 potentiates macrophage fusion. DAP12 regulates expression of macrophage fusion mediators including DC-STAMP and Cadherin 1. Genetic approach (DAP12-/-, TREM-2-/-, Syk inhibition), macrophage fusion assay, gene expression analysis, DAP12 overexpression Science Signaling High 18957693
2008 E-selectin engagement of PSGL-1 signals through the Src family kinase Fgr and ITAM-containing adaptors DAP12 and FcRγ to activate Syk and p38 MAPK, enabling slow leukocyte rolling. Neutrophils from Tyrobp-/-Fcrg-/- mice cannot sustain slow rolling, cannot phosphorylate Syk or p38 MAPK, and show impaired G-alpha-i-independent peritoneal recruitment in vivo. Gene-deficient mouse neutrophils, flow chamber rolling assay, intravital microscopy, phosphorylation assays, mixed chimeric mice, peritonitis model The Journal of Experimental Medicine High 18794338
2009 DAP12 is essential for M-CSF-induced macrophage proliferation and survival. M-CSF signaling through CSF-1R induces stabilization and nuclear translocation of β-catenin to activate cell-cycle genes; DAP12 is required for phosphorylation and nuclear accumulation of β-catenin. DAP12-deficient mice have fewer microglia in defined CNS areas, and DAP12-deficient progenitors regenerate myeloid cells inefficiently after bone marrow transplantation. DAP12-/- mouse macrophage proliferation/survival assays, β-catenin phosphorylation and nuclear translocation assays, bone marrow transplantation, microglial quantification Nature Immunology High 19503107
2010 TREM2-DAP12 signaling activates PI3K, ERK1/2, and Vav3, and mobilizes intracellular calcium and actin reorganization. The adaptor molecule DAP10 plays a key role in recruiting PI3K to the TREM2-DAP12 signaling complex. SHIP1 inhibits TREM2-DAP12 signaling by binding DAP12 in an SH2 domain-dependent manner, directly blocking PI3K recruitment. TREM2 ligation assays, PI3K activation assay, ERK assay, calcium imaging, actin reorganization, co-immunoprecipitation (SHIP1-DAP12), SH2 domain mutant SHIP1 analysis Science Signaling High 20484116
2010 In DAP12-deficient osteoclasts generated on osteoblasts, differentiation occurs normally but the osteoclast cytoskeleton is dysfunctional, preventing transmigration through the osteoblast layer and bone resorption. OSCAR (FcRγ co-receptor) overexpression partially rescues the abnormal cytoskeleton of DAP12-/- osteoclasts grown on bone but not on osteoblasts, indicating cytoskeletal dysfunction is the dominant consequence of DAP12 deficiency. Osteoclast/osteoblast co-culture assay, cytoskeletal imaging, OSCAR-FLAG overexpression rescue in DAP12-/- osteoclasts Journal of Cell Science High 20720152
2011 In B cells, DAP12-associated MAIR-II (CD300d) negatively regulates BCR-mediated proliferation. A chimeric MAIR-II-DAP12 receptor recruits SHP-1 after BCR stimulation to suppress B cell activation. DAP12-deficient mice show elevated serum autoantibodies and enhanced humoral immune responses. DAP12-/- and MAIR-II-/- B cell proliferation assays, chimeric receptor reconstitution, SHP-1 co-immunoprecipitation after BCR stimulation, in vivo antibody measurements The Journal of Experimental Medicine High 21727189
2011 DAP12 silencing in liver myeloid dendritic cells promotes their maturation, enhancing TNF-α, IL-6, and IL-12p70 production and reducing IL-10 secretion. DAP12 silencing correlates with decreased STAT3 phosphorylation and diminished IRAK-M expression, indicating DAP12 maintains liver DC immaturity via STAT3/IRAK-M-dependent suppression of TLR signaling. siRNA knockdown of DAP12 in liver DCs, cytokine measurement, STAT3 phosphorylation assay, IRAK-M expression analysis, T cell allostimulation assay Journal of Immunology Medium 21257958
2012 Siglec-15 associates with DAP12 through its Lys-272 transmembrane residue and signals via Syk to regulate functional osteoclast formation and bone resorption. Siglec-15 V-set domain recognition of sialylated glycans and its DAP12 association are both required for its function. Siglec-15 links the RANK-NFAT2 and DAP12 signaling pathways in osteoclasts. Lys272 mutagenesis, co-immunoprecipitation (Siglec-15/Syk via DAP12), shRNA knockdown, multinucleation and bone resorption assays, chimeric receptor rescue The Journal of Biological Chemistry High 22451653
2012 Siglec-15 associates with DAP12 at its Lys-274 transmembrane residue and transduces a signal to Syk, leading to enhanced TGF-β secretion from monocytes/macrophages upon recognition of tumor-associated sialyl-Tn antigen. Substitution of Lys-274 to Ala or Syk inhibitor treatment abolishes this enhanced TGF-β production. Siglec-15/DAP12 interaction via K274A mutagenesis, Syk inhibitor treatment, co-culture model with sTn-positive cancer cells, TGF-β ELISA Glycobiology High 23035012
2014 αvβ3 integrin occupancy induces phosphorylation of DAP12, which is essential for osteoclast function. Co-deletion of αvβ3 and DAP12 causes severe osteopetrosis with profound osteoclast dysfunction, more severe than either single KO. FcRγ requires the osteoclast αvβ3 integrin to compensate for DAP12 deficiency; OSCAR-activated FcRγ cannot rescue Syk phosphorylation in DAP12/β3 double-null osteoclasts. αvβ3/DAP12 double-KO mice, Syk phosphorylation assay, OSCAR activation rescue experiment, histomorphometry/microCT The Journal of Cell Biology High 25547154
2015 DAP12 is required for both nerve injury- and intrathecal CSF1-induced upregulation of pain-related microglial genes and mechanical hypersensitivity, but not for CSF1-induced microglial proliferation. DAP12 acts downstream of CSF1R in a neuropathic pain pathway. DAP12-deficient mice in nerve injury and intrathecal CSF1 injection models, mechanical hypersensitivity testing, microglial proliferation assay, gene expression profiling Nature Neuroscience High 26642091
2015 DAP12 stabilizes the C-terminal fragment of TREM2 (TREM2-CTF), a γ-secretase substrate. Co-expression of DAP12 with TREM2 selectively increases TREM2-CTF levels. A DAP12 mutant with disrupted TREM2 interaction fails to stabilize TREM2-CTF. Silencing of either Trem2 or Dap12 exacerbates LPS-induced pro-inflammatory responses. Co-expression/co-IP, DAP12 interaction-disrupting mutant, gene silencing (Trem2/Dap12), LPS-induced inflammatory cytokine assay The Journal of Biological Chemistry High 25957402
2015 DAP12 expression in tissue-resident alveolar macrophages promotes neutrophil recruitment during lung ischemia/reperfusion injury by supporting macrophage survival and local production of neutrophil chemoattractants (CXCL2). Donor but not recipient DAP12 deficiency is protective; intravital imaging demonstrated a transendothelial migration defect into DAP12-deficient lungs rescuable by CXCL2 administration. Lung transplant IRI mouse model, donor vs. recipient DAP12 KO experiment, intravital imaging, CXCL2 rescue, macrophage survival assay Journal of Immunology High 25762783
2016 TREM2/DAP12 signaling in microglia exacerbates neuropathic pain by inducing proinflammatory cytokine secretion. Dap12-deficient mice show significantly suppressed nerve injury-induced proinflammatory cytokine expression and pain behaviors. Intrathecal TREM2 agonistic antibody-induced proinflammatory responses and pain were absent in Dap12-deficient mice. Dap12-/- mice in spinal nerve injury model, intrathecal TREM2 agonistic antibody injection, cytokine expression assay, mechanical hypersensitivity testing The Journal of Neuroscience High 27798193
2017 TREM2/DAP12 complex suppresses LPS-induced microglial hyperactivation via the JNK signaling pathway. LPS downregulates Trem2 expression via JNK and NF-κB, creating a positive inflammatory feedback loop. DAP12's anti-inflammatory role requires the presence of TREM2. Murine microglia LPS stimulation, Dap12/Trem2 siRNA knockdown, JNK pathway inhibition, cytokine assays, expression analysis Frontiers in Aging Neuroscience Medium 28680398
2017 TYROBP deficiency in a mouse model of early Alzheimer's pathology (APP/PSEN1;Tyrobp-/-) attenuates electrophysiological abnormalities and learning behavior deficits, reduces tau phosphorylation severity and neuritic dystrophy, and alters Cd33 expression. TYROBP acts as an adaptor for TREM2, CD33, and CR3 receptors in microglia. APP/PSEN1;Tyrobp-/- double-mutant mice, electrophysiology, behavioral testing, immunohistochemistry, transcriptomics Acta Neuropathologica High 28612290
2018 TYROBP deficiency in a tauopathy mouse model (MAPTP301S;Tyrobp-/-) normalizes learning behavior and synaptic electrophysiological function and reduces complement C1q levels, despite paradoxically increasing tau spreading and phosphorylation biomarkers. This dissociation suggests TYROBP-mediated C1q reduction underlies neuroprotection. MAPTP301S;Tyrobp-/- mice, behavioral testing, LTP electrophysiology, C1q immunohistochemistry, tau pathology assays Molecular Psychiatry High 30283031
2007 The zebrafish activating immune receptor Nitr9L preferentially partners with a zebrafish ortholog of Dap12. Crosslinking the Nitr9L-Dap12 complex activates the PI3K→AKT→ERK pathway, indicating that the DAP12-based activating pathway is conserved in bony fish. Co-immunoprecipitation, crosslinking activation assay, PI3K/AKT/ERK pathway analysis Immunogenetics Medium 17891481
2007 DAP12 paradoxically down-modulates plasmacytoid dendritic cell (pDC) cytokine production during MCMV infection. DAP12-deficient mice have increased pDC numbers in the periphery and enhanced IFN-αβ and IL-12 production upon MCMV infection or CpG treatment. The inhibitory effect on IL-12 (but not IFN-αβ in MCMV) is pDC-intrinsic, while homeostatic effects are indirect. DAP12-deficient mice, MCMV infection model, CpG treatment, mixed bone marrow chimeras (cell-intrinsic vs. extrinsic), intracellular cytokine staining, in vitro Flt3L differentiation Journal of Immunology High 16920926
2011 Btk (Bruton's tyrosine kinase) is phosphorylated upon TREM-1 triggering downstream of DAP12 and acts as a positive regulator in the TREM-1/DAP12 pathway. Btk knockdown reduces Erk1/2 and PLCγ1 phosphorylation and Ca²⁺ mobilization after TREM-1 stimulation, and impairs TNF-α and IL-8 production. Intact membrane localization and functional kinase domain of Btk are required. shRNA knockdown of Btk, Btk kinase/membrane localization mutants, Erk1/2 and PLCγ1 phosphorylation assay, Ca²⁺ mobilization, cytokine ELISA, Btk-/- BMDC analysis Blood High 21659545
2007 The DAP12 promoter is directly controlled by the transcription factor PU.1 via evolutionarily conserved PU.1 binding sites in the proximal -104/+118 region. PU.1 knockdown by RNAi reduces endogenous DAP12 expression; re-expression/activation of PU.1 in PU.1-/- progenitors induces DAP12 transcription. PU.1 binding was confirmed by EMSA and ChIP. Promoter deletion assays, site-directed mutagenesis of PU.1 sites, EMSA, chromatin immunoprecipitation (ChIP), PU.1 RNAi knockdown, PU.1-/- progenitor reconstitution Journal of Leukocyte Biology High 17827340
2023 Single-nucleus RNA-sequencing of DAP12-deficient NHD patient brains revealed a unique microglia signature indicating heightened RUNX1, STAT3, and TGF-β signaling pathways that mediate wound-healing responses. This correlated with wound healing signatures in astrocytes, impaired myelination in oligodendrocytes, and vascular abnormalities in pericytes. DAP12-deficient mice did not recapitulate these microglial defects, suggesting human-specific pathology. Single-nucleus RNA-sequencing of human NHD brain specimens, comparison with DAP12-deficient mouse brain Nature Immunology Medium 36658241
2019 Cell-surface NMHC-IIA recognizes sialic acids on sialylated RNA viruses and interacts with DAP12 via its transmembrane region to recruit Syk, leading to suppressed proinflammatory responses. This NMHC-IIA–DAP12–Syk pathway also inhibits LPS-induced proinflammatory signaling. Co-immunoprecipitation (NMHC-IIA with DAP12), Syk recruitment assay, sialic acid recognition studies, LPS suppression assay, viral infection models mBio Medium 31064828
2016 A rare TYROBP coding variant (p.D50_L51ins14) identified in early-onset Alzheimer's disease patients leads to a profound reduction of TREM2 expression in vitro, demonstrating that certain TYROBP mutations disrupt TREM2 expression. Exome sequencing, in vitro overexpression of mutant TYROBP with TREM2 expression measurement Neurobiology of Aging Medium 27658901

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature 722 9490415
2015 Injured sensory neuron-derived CSF1 induces microglial proliferation and DAP12-dependent pain. Nature neuroscience 458 26642091
1998 Association of DAP12 with activating CD94/NKG2C NK cell receptors. Immunity 432 9655483
2001 A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells. The Journal of experimental medicine 384 11602640
2000 Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts. Nature genetics 370 10888890
2004 The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional osteoclasts through the Syk tyrosine kinase. Proceedings of the National Academy of Sciences of the United States of America 363 15073337
2010 TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1. Science signaling 348 20484116
2003 Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice. The Journal of clinical investigation 285 12569157
2009 Macrophage colony-stimulating factor induces the proliferation and survival of macrophages via a pathway involving DAP12 and beta-catenin. Nature immunology 260 19503107
2003 DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features. The Journal of experimental medicine 251 12925681
2018 Microglial TREM2/DAP12 Signaling: A Double-Edged Sword in Neural Diseases. Frontiers in cellular neuroscience 241 30127720
1998 Ly-49D and Ly-49H associate with mouse DAP12 and form activating receptors. Journal of immunology (Baltimore, Md. : 1950) 238 9647200
2007 Activating and inhibitory functions of DAP12. Nature reviews. Immunology 221 17220916
2018 Microglia and Aging: The Role of the TREM2-DAP12 and CX3CL1-CX3CR1 Axes. International journal of molecular sciences 220 29361745
2006 Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis. Nature cell biology 216 16715077
2015 DAP12-based activating chimeric antigen receptor for NK cell tumor immunotherapy. Journal of immunology (Baltimore, Md. : 1950) 210 25740942
2000 DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming. Immunity 191 11021532
2000 DAP10 and DAP12 form distinct, but functionally cooperative, receptor complexes in natural killer cells. The Journal of experimental medicine 190 11015446
2004 Impaired synaptic function in the microglial KARAP/DAP12-deficient mouse. The Journal of neuroscience : the official journal of the Society for Neuroscience 185 15601948
2005 The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2. Neurology 184 15883308
1999 Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells. Proceedings of the National Academy of Sciences of the United States of America 170 10449773
2007 The TREM-1/DAP12 pathway. Immunology letters 169 18192027
2008 PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcR gamma to induce slow leukocyte rolling. The Journal of experimental medicine 168 18794338
1998 DAP12-mediated signal transduction in natural killer cells. A dominant role for the Syk protein-tyrosine kinase. The Journal of biological chemistry 167 9830044
2000 The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function. Immunology today 163 11114420
2001 Cloning and characterization of a novel mouse myeloid DAP12-associated receptor family. European journal of immunology 157 11241283
2012 The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway. Glycobiology 150 23035012
2004 Distribution and signaling of TREM2/DAP12, the receptor system mutated in human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy dementia. The European journal of neuroscience 137 15548205
2016 TREM2/DAP12 Signal Elicits Proinflammatory Response in Microglia and Exacerbates Neuropathic Pain. The Journal of neuroscience : the official journal of the Society for Neuroscience 136 27798193
2005 TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 136 16418779
2000 Combined natural killer cell and dendritic cell functional deficiency in KARAP/DAP12 loss-of-function mutant mice. Immunity 135 11021533
2000 Cutting edge: signal-regulatory protein beta 1 is a DAP12-associated activating receptor expressed in myeloid cells. Journal of immunology (Baltimore, Md. : 1950) 130 10604985
2022 Microglial TYROBP/DAP12 in Alzheimer's disease: Transduction of physiological and pathological signals across TREM2. Molecular neurodegeneration 129 36002854
1998 Gene structure, expression pattern, and biological activity of mouse killer cell activating receptor-associated protein (KARAP)/DAP-12. The Journal of biological chemistry 126 9852069
2004 Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy--PLOSL): a dementia associated with bone cystic lesions. From clinical to genetic and molecular aspects. Cellular and molecular neurobiology 125 15049507
2015 DAP12 Stabilizes the C-terminal Fragment of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) and Protects against LPS-induced Pro-inflammatory Response. The Journal of biological chemistry 118 25957402
2002 TREM-1, MDL-1, and DAP12 expression is associated with a mature stage of myeloid development. Molecular immunology 115 11922939
2005 KARAP/DAP12/TYROBP: three names and a multiplicity of biological functions. European journal of immunology 111 15884055
2009 The expanding roles of ITAM adapters FcRgamma and DAP12 in myeloid cells. Immunological reviews 107 19909355
2005 Silencing human NKG2D, DAP10, and DAP12 reduces cytotoxicity of activated CD8+ T cells and NK cells. Journal of immunology (Baltimore, Md. : 1950) 107 16339517
2008 DAP12 couples c-Fms activation to the osteoclast cytoskeleton by recruitment of Syk. Molecular cell 106 18691974
2003 The signaling adapter protein DAP12 regulates multinucleation during osteoclast development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 100 14969392
2017 Deficiency of TYROBP, an adapter protein for TREM2 and CR3 receptors, is neuroprotective in a mouse model of early Alzheimer's pathology. Acta neuropathologica 97 28612290
2008 Essential role of DAP12 signaling in macrophage programming into a fusion-competent state. Science signaling 97 18957693
2015 Generation of Potent T-cell Immunotherapy for Cancer Using DAP12-Based, Multichain, Chimeric Immunoreceptors. Cancer immunology research 96 25941351
2005 Dap12 and Trem2, molecules involved in innate immunity and neurodegeneration, are co-expressed in the CNS. Neurobiology of disease 95 15686960
2003 High dose M-CSF partially rescues the Dap12-/- osteoclast phenotype. Journal of cellular biochemistry 92 14624447
2015 The TREM2-DAP12 signaling pathway in Nasu-Hakola disease: a molecular genetics perspective. Research and reports in biochemistry 90 26478868
2013 Structure, expression pattern and biological activity of molecular complex TREM-2/DAP12. Human immunology 85 23459077
2014 TYROBP in Alzheimer's disease. Molecular neurobiology 84 25052481
2012 Siglec-15 protein regulates formation of functional osteoclasts in concert with DNAX-activating protein of 12 kDa (DAP12). The Journal of biological chemistry 83 22451653
2000 Association of signal-regulatory proteins beta with KARAP/DAP-12. European journal of immunology 83 10940905
2008 Developmental regulation of TREM2 and DAP12 expression in the murine CNS: implications for Nasu-Hakola disease. Neurochemical research 82 18404378
2002 Pivotal role of KARAP/DAP12 adaptor molecule in the natural killer cell-mediated resistance to murine cytomegalovirus infection. The Journal of experimental medicine 80 11927627
2010 Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis. The Journal of experimental medicine 79 20212065
2006 DAP12: an adapter protein with dual functionality. Immunological reviews 79 17100880
2017 TREM2/DAP12 Complex Regulates Inflammatory Responses in Microglia via the JNK Signaling Pathway. Frontiers in aging neuroscience 72 28680398
2016 TYROBP genetic variants in early-onset Alzheimer's disease. Neurobiology of aging 70 27658901
2017 Opposing effects of progranulin deficiency on amyloid and tau pathologies via microglial TYROBP network. Acta neuropathologica 68 28070672
2004 Stimulatory killer Ig-like receptors modulate T cell activation through DAP12-dependent and DAP12-independent mechanisms. Journal of immunology (Baltimore, Md. : 1950) 68 15356118
2005 Brain and bone damage in KARAP/DAP12 loss-of-function mice correlate with alterations in microglia and osteoclast lineages. The American journal of pathology 67 15632019
2003 Selective activation of the c-Jun NH2-terminal protein kinase signaling pathway by stimulatory KIR in the absence of KARAP/DAP12 in CD4+ T cells. The Journal of experimental medicine 61 12591902
2011 TREM-1 and DAP12 expression in monocytes of patients with severe psychiatric disorders. EGR3, ATF3 and PU.1 as important transcription factors. Brain, behavior, and immunity 59 21421043
2004 Loss or mismatch of MHC class I is sufficient to trigger NK cell-mediated rejection of resting lymphocytes in vivo - role of KARAP/DAP12-dependent and -independent pathways. European journal of immunology 58 15162434
2015 DAP12 expression in lung macrophages mediates ischemia/reperfusion injury by promoting neutrophil extravasation. Journal of immunology (Baltimore, Md. : 1950) 56 25762783
2018 Integrative approach to sporadic Alzheimer's disease: deficiency of TYROBP in a tauopathy mouse model reduces C1q and normalizes clinical phenotype while increasing spread and state of phosphorylation of tau. Molecular psychiatry 55 30283031
2004 CD200 receptor family members represent novel DAP12-associated activating receptors on basophils and mast cells. The Journal of biological chemistry 51 15471863
2006 DAP12 signaling regulates plasmacytoid dendritic cell homeostasis and down-modulates their function during viral infection. Journal of immunology (Baltimore, Md. : 1950) 48 16920926
2004 IL-4 confers NK stimulatory capacity to murine dendritic cells: a signaling pathway involving KARAP/DAP12-triggering receptor expressed on myeloid cell 2 molecules. Journal of immunology (Baltimore, Md. : 1950) 48 15128777
2023 Human early-onset dementia caused by DAP12 deficiency reveals a unique signature of dysregulated microglia. Nature immunology 47 36658241
2017 Gene co-expression networks identify Trem2 and Tyrobp as major hubs in human APOE expressing mice following traumatic brain injury. Neurobiology of disease 47 28502803
1999 DAP12: a key accessory protein for relaying signals by natural killer cell receptors. The international journal of biochemistry & cell biology 46 10404635
2011 Btk is a positive regulator in the TREM-1/DAP12 signaling pathway. Blood 43 21659545
2006 Regulation of Ly49D/DAP12 signal transduction by Src-family kinases and CD45. Journal of immunology (Baltimore, Md. : 1950) 42 16709819
2021 TYROBP, TLR4 and ITGAM regulated macrophages polarization and immune checkpoints expression in osteosarcoma. Scientific reports 40 34588497
2014 Absence of Dap12 and the αvβ3 integrin causes severe osteopetrosis. The Journal of cell biology 39 25547154
2007 The zebrafish activating immune receptor Nitr9 signals via Dap12. Immunogenetics 39 17891481
2004 Differential regulation of DAP12 and molecules associated with DAP12 during host responses to mycobacterial infection. Infection and immunity 39 15102754
1998 Assignment of the locus for PLO-SL, a frontal-lobe dementia with bone cysts, to 19q13. American journal of human genetics 39 9463329
2020 Bilberry anthocyanins improve neuroinflammation and cognitive dysfunction in APP/PSEN1 mice via the CD33/TREM2/TYROBP signaling pathway in microglia. Food & function 38 32003387
2022 Curcumin-Attenuated TREM-1/DAP12/NLRP3/Caspase-1/IL1B, TLR4/NF-κB Pathways, and Tau Hyperphosphorylation Induced by 1,2-Diacetyl Benzene: An in Vitro and in Silico Study. Neurotoxicity research 36 35781221
2004 Human NKG2F is expressed and can associate with DAP12. Molecular immunology 36 15140575
2007 Dap12 expression in activated microglia from retinoschisin-deficient retina and its PU.1-dependent promoter regulation. Journal of leukocyte biology 35 17827340
2008 A critical role for DAP10 and DAP12 in CD8+ T cell-mediated tissue damage in large granular lymphocyte leukemia. Blood 34 19075187
2000 The role of the DAP12 signal in mouse myeloid differentiation. Journal of immunology (Baltimore, Md. : 1950) 34 11034384
2020 A Humanized Lym-1 CAR with Novel DAP10/DAP12 Signaling Domains Demonstrates Reduced Tonic Signaling and Increased Antitumor Activity in B-Cell Lymphoma Models. Clinical cancer research : an official journal of the American Association for Cancer Research 32 32273277
2015 Variable expression of microglial DAP12 and TREM2 genes in Nasu-Hakola disease. Neurogenetics 32 26001891
2019 Nonmuscle Myosin Heavy Chain IIA Recognizes Sialic Acids on Sialylated RNA Viruses To Suppress Proinflammatory Responses via the DAP12-Syk Pathway. mBio 31 31064828
2011 DAP12 promotes IRAK-M expression and IL-10 production by liver myeloid dendritic cells and restrains their T cell allostimulatory ability. Journal of immunology (Baltimore, Md. : 1950) 29 21257958
2010 Cytoskeletal dysfunction dominates in DAP12-deficient osteoclasts. Journal of cell science 29 20720152
2020 Siglecs that Associate with DAP12. Advances in experimental medicine and biology 28 32152949
2014 Human NKG2E is expressed and forms an intracytoplasmic complex with CD94 and DAP12. Journal of immunology (Baltimore, Md. : 1950) 28 24935923
2011 The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive immune responses. The Journal of experimental medicine 27 21727189
2000 DAP12 and KAP10 (DAP10)-novel transmembrane adapter proteins of the CD3zeta family. Immunologic research 27 10945225
2020 Non-pathological roles of microglial TREM2/DAP12: TREM2/DAP12 regulates the physiological functions of microglia from development to aging. Neurochemistry international 26 33049336
2018 Integrated biology approach reveals molecular and pathological interactions among Alzheimer's Aβ42, Tau, TREM2, and TYROBP in Drosophila models. Genome medicine 26 29598827
2018 TLR4 Promotes and DAP12 Limits Obesity-Induced Osteoarthritis in Aged Female Mice. JBMR plus 26 31044181
2013 Role of TREM1-DAP12 in renal inflammation during obstructive nephropathy. PloS one 26 24358193
2024 Effects of methionine deficiency on B7H3-DAP12-CAR-T cells in the treatment of lung squamous cell carcinoma. Cell death & disease 24 38182561
2003 Role of DAP12 in innate and adaptive immune responses. Current pharmaceutical design 24 12570670

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